Adaptive landscapes and protein evolution
Adaptive landscapes and protein evolution
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DOI：
10.1073/pnas.0906192106
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发表时间：
2010-01-26
影响因子：
11.1
通讯作者：
Hartl, Daniel L.
中科院分区：
文献类型：
--
作者：
Carneiro, Mauricio;Hartl, Daniel L.
强选择下的蛋白质进化原理非常重要，因为最近进化出了对杀虫剂、抗生素和疫苗的抗性。一种实验方法侧重于研究突变蛋白和突变位点的所有组合，这些突变位点可能是抗性进化途径中的中间体。在携带每种工程蛋白质的生物体中，估计蛋白质功能的量度或适应性的代理。蛋白质序列和适应度之间的对应关系被广泛称为适应度景观或适应性景观。在这里，我们研究了一些经验适应度景观，并将其与随机分配适应度的模拟景观进行比较。我们发现，突变位点在真实的蛋白质显示出显着更多的加和性比随机模拟。高度的可加性反映在适应性景观的汇总统计中，称为“粗糙度”，对于迄今为止研究的实际蛋白质，它位于随机景观的最小0.5%尾部。
The principles governing protein evolution under strong selection are important because of the recent history of evolved resistance to insecticides, antibiotics, and vaccines. One experimental approach focuses on studies of mutant proteins and all combinations of mutant sites that could possibly be intermediates in the evolutionary pathway to resistance. In organisms carrying each of the engineered proteins, a measure of protein function or a proxy for fitness is estimated. The correspondence between protein sequence and fitness is widely known as a fitness landscape or adaptive landscape. Here, we examine some empirical fitness landscapes and compare them with simulated landscapes in which the fitnesses are randomly assigned. We find that mutant sites in real proteins show significantly more additivity than those obtained from random simulations. The high degree of additivity is reflected in a summary statistic for adaptive landscapes known as the "roughness," which for the actual proteins so far examined lies in the smallest 0.5% tail of random landscapes.